Carlo Nunes

Improvement in orofacial granulomatosis on a cinnamon- and benzoate-free diet.

Background: Orofacial granulomatosis (OFG) is a chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Although the cause remains unknown, there is evidence for involvement of a dietary allergen. Patch testing has related responses to cinnamon and benzoate to the symptoms of OFG, with improvement obtained through exclusion diets. However, an objective assessment of the effect of a cinnamon‐ and benzoate‐free diet (CB‐free diet) as primary treatment for OFG has not previously been performed. Thus, this study was undertaken to investigate the benefits of a CB‐free diet as first‐line treatment of patients with OFG. Materials and Methods: Thirty‐two patients with a confirmed diagnosis of OFG were identified from a combined oral medicine/gastroenterology clinic. All had received a CB‐free diet as primary treatment for a period of 8 weeks. Each patient underwent a standardized assessment of the oral cavity to characterize the number of sites affected and the type of inflammation involved before and after diet. Results: There was a significant improvement in oral inflammation in patients on the diet after 8 weeks. Both global oral and lip inflammatory scores improved (P < 0.001), and there was significant improvement in both lip and oral site and activity involvement. However, improvement in lip activity was less marked than oral activity. Response to a CB‐free diet did not appear to be site specific. A history of OFG‐associated gut involvement did not predict a response to the diet. Conclusions: The impact of dietary manipulation in patients with OFG can be significant, particularly with regard to oral inflammation. With the disease most prevalent in the younger population, a CB‐free diet can be recommended as primary treatment. Subsequent topical or systemic immunomodulatory therapy may then be avoided or used as second line.

Oro-facial granulomatosis: Crohn's disease or a new inflammatory bowel disease?

Background: Oro‐facial granulomatosis (OFG) is a rare chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Histologically, OFG resembles Crohns disease (CD), and a number of patients with CD have oral involvement identical to OFG. However, the exact relationship between OFG and CD remains unknown. Methods: Thirty‐five patients with OFG and no gut symptoms were identified from a combined oral medicine/gastroenterology clinic. All underwent a standardized assessment of the oral cavity and oral mucosal biopsy to characterize the number of sites affected and the type of inflammation involved. Hematological and biochemical parameters were also recorded. All 35 patients underwent ileocolonoscopy and biopsy to assess the presence of coexistent intestinal inflammation. Results: Ileal or colonic abnormalities were detected in 19/35 (54%) cases. From gut biopsies, granulomas were present in 13/19 cases (64%). An intestinal abnormality was significantly more likely if the age of OFG onset was less than 30 years (P = 0.01). Those with more severe oral inflammation were also more likely to have intestinal inflammation (P = 0.025), and there was also a correlation between the histologic severity of oral inflammation and the histologic severity of gut inflammation (P = 0.047). No relationship was found between any blood parameter and intestinal involvement. Conclusions: Endoscopic and histologic intestinal abnormalities are common in patients with OFG with no gastrointestinal symptoms. Younger patients with OFG are more likely to have concomitant intestinal involvement. In these patients, granulomas are more frequent in endoscopic biopsies than reported in patients with documented CD. OFG with associated intestinal inflammation may represent a separate entity in which granulomatous inflammation occurs throughout the gastrointestinal tract in response to an unknown antigen or antigens.

Distinguishing orofacial granulomatosis from crohn's disease: Two separate disease entities?

Background: Orofacial granulomatosis (OFG) is a rare chronic inflammatory disease of unknown etiology sharing histological features with Crohns disease (CD). This study aimed to 1) define the clinical presentation of OFG, 2) establish differentiating features for those with CD, 3) examine if onset of OFG is predictive of CD, and 4) establish differentiating features for children. Methods: Data were extracted from medical notes (n = 207) for demographics, clinical features, blood parameters, diagnosis of CD, and treatments for patients with OFG. Results: Ninety‐seven patients (47%) were female. The lips (184/203; 91%) and buccal mucosa (151/203; 74%) were mainly affected. Forty‐six (22%) had intestinal CD. Ulcers (24/46; 46% versus 29/159; 15%, P = <0.001) were more common in patients with CD as was a raised C‐reactive protein (24/33; 73% versus 60/122; 49%, P = 0.016) and abnormal full blood count (19/41; 46% versus 35/150; 23%). The buccal‐sulcus (12/44; 27% versus 20/158; 13%, P = 0.019) was more often affected in those with CD. Half the patients with CD were diagnosed prior to onset of OFG. The remainder were diagnosed after. The incidence of CD is similar for children (16/69; 23%) and adults (29/132; 22%), although oral onset in childhood is more likely to occur prior to diagnosis of CD. Conclusions: OFG mainly presents in young adults with lip and buccal involvement. Abnormalities in inflammatory markers, hematology and oral features of ulceration, and buccal‐sulcal involvement are factors more commonly associated with CD. Initial presentation of OFG does not necessarily predict development of CD, although this is more likely in childhood. (Inflamm Bowel Dis 2011;)

Subepithelial dendritic B cells in orofacial granulomatosis

Background: Orofacial granulomatosis (OFG) is a chronic, disfiguring, granulomatous inflammation of the lips and oral mucosa. The pathogenesis is unknown, but it has been linked previously to Crohns disease (CD) and more recently to dietary sensitivity. The oral mucosa is an immunologically responsive site associated with the generation of protective mucosal and systemic immune responses to vaccination and also hyperresponsiveness to allergens in some individuals. Classically, immune responses in oral mucosa are considered to be mediated by mucosa‐associated lymphoid tissues (MALT), secondary lymphoid follicles that are intimately associated with epithelia. Methods: Immunohistochemistry was used to investigate the inflammatory infiltrate in OFG and control tissue samples. Polymerase chain reaction (PCR), cloning of PCR products, and sequencing were used to characterize the local immunoglobulin gene profile in OFG. Results: We describe large, active, dendritic B cells in oral mucosa that were not associated with any organized lymphoid tissues in the local subepithelial microenvironment. They express activation induced cytidine deaminase, which is essential for immunoglobulin gene diversification by somatic hypermutation and class switch recombination. IgE is also expressed by these B cells. They do not align with any other previously described B‐cell subset in secondary lymphoid tissues in terms of morphology, proliferative activity, or phenotype. Conclusions: These subepithelial dendritic B cells may contribute to the immune responsiveness of the oral mucosa, including IgE‐mediated allergic responses. In patients with OFG, further understanding of the role these cells play in oral immunity may lead to novel therapeutic possibilities. (Inflamm Bowel Dis 2010)

OC-095 A clinical overview of the presentation and management of orofacial granulomatosis in a combined oral medicine and gastroenterology clinic

Introduction Orofacial granulomatosis (OFG) is a rare chronic inflammatory disease of unknown aetiology sharing histological features with gut Crohns disease (CD). A notes review of 207 patients with OFG aimed to define the common presentation of this condition and establish differentiating features between those with and without concurrent diagnosis of CD. Methods Data were extracted for age of onset, gender, clinical features, blood parameters, concurrent CD and treatments used. Diagnosis of CD was established by standard criteria. Results Ninety-seven out of 207 patients (47%) were female. Median age of disease onset was 23 years (range 2–73 years). Referrals were mainly sourced from maxillo-facial surgeons (31%) and gastroenterologists (19%). The buccal mucosa (74%) and lower lip (68%) were the most common sites involved followed by gingivae (63.5%) and upper lip (61%). Forty-six (22%) had CD. Ulcers (46% vs 15%, p<0.001) and mucosal scarring (20% vs 5%, p<0.001) were more common in patients with CD than in those without as was a raised C reactive protein (73% vs 49%, p=0.016), abnormal full blood counts (46% vs 23%) and low haemoglobin (31% vs 11%). The sulcus (27% vs 13%, p=0.019) and fauces (4% vs 0%, p=0.008) were significantly more likely to be affected in those with CD. Of the patients with concurrent CD, half were diagnosed with this prior to onset of OFG symptoms. Conversely 42.5% had OFG symptoms prior to diagnosis of CD. The remaining patients (7.5%) presented with symptoms and were diagnosed with CD within the same year. The predominant treatment used (86%) was the cinnamon and benzoate free diet. Topical treatments including antifungal and steroidal creams, ointments, mouthwashes and intralesional steroid injections were used in 64% of cases. Azathioprine was used in 39% of patients and anti TNF α therapy in 7.5% of patients. Only 3% of patients required cheiloplasty. Conclusion OFG most commonly presents with buccal and lower lip involvement. Abnormalities in inflammatory markers, haematinic deficiencies and oral presentation of ulceration and scarring are all factors which can increase the likelihood of concurrent CD. Initial presentation of OFG is not necessarily predictive of further development of CD.